tbuckley/cabot-search huggingface dataset:
Comment on ‘Effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on survival and recurrence rates in advanced gastric cancer – a systematic review and meta-analysis’
Authors: Xian-Wen Liang, Hui Liu, Jin-Cai Wu
Journal: International Journal of Surgery (2023)

aDepartment of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) bDepartment of Interventional Radiology, Central South University, Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan Province, People's Republic of China Published online ■ ■ *Corresponding author. Address: Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan Province 570311, People's Republic of China.Tel.: +861 888 976 5723. E-mail:[email protected] (J.-C. Wu). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development
Authors: Fitzwilliam Seibertz, Tony Rubio, Robin Springer, Fiona Popp, Melanie Ritter, Aiste Liutkute, Lena Bartelt, Lea Stelzer, Fereshteh Haghighi, Jan Pietras, Hendrik Windel, Núria Díaz i Pedrosa, Markus Rapedius, Yannic Doering, Richard Solano, Robin Hindmarsh, Runzhu Shi, Malte Tiburcy, Tobias Bruegmann, Ingo Kutschka, Katrin Streckfuss-Bömeke, George Kensah, Lukas Cyganek, Wolfram H Zimmermann, Niels Voigt
Journal: Cardiovascular Research (2023)

Atrial fibrillation (AF) is associated with tachycardia-induced cellular electrophysiology alterations which promote AF chronification and treatment resistance. Development of novel antiarrhythmic therapies is hampered by the absence of scalable experimental human models that reflect AF-associated electrical remodelling. Therefore, we aimed to assess if AF-associated remodelling of cellular electrophysiology can be simulated in human atrial-like cardiomyocytes derived from induced pluripotent stem cells in the presence of retinoic acid (iPSC-aCM), and atrial-engineered human myocardium (aEHM) under short term (24 h) and chronic (7 days) tachypacing (TP).
Optimal tentative abdominal closure for open abdomen: a multicenter retrospective observational study (OPTITAC study)
Authors: Ryo Yamamoto, Shunsuke Kuramoto, Masayuki Shimizu, Hiroharu Shinozaki, Tasuku Miyake, Yoshihiko Sadakari, Kazuhiko Sekine, Yasushi Kaneko, Ryo Kurosaki, Kiyoshi Koizumi, Takayuki Shibusawa, Yoshihiko Sakurai, Sota Wakahara, Junichi Sasaki
Journal: International Journal of Surgery (2023)

Background: Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure. Materials and Methods: A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (&lt;50, 50–100, or &gt;100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics. Results: Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (&gt;100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50–0.69), P =0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30–82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00–0.50)]. Conclusion: High negative pressure (&gt;100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.
Long-term outcomes of mitral valve replacement in dialysis patients: evidence from a nationwide database
Authors: Kelvin J. Yang, Hsun-Yi Fu, Chia-Jui Chang, Ting-Chuan Wang, Chih-Hsien Wang, Nai-Kuan Chou, I-Hui Wu, Ron-Bin Hsu, Shu-Chien Huang, Hsi-Yu Yu, Yih-Sharng Chen, Nai-Hsin Chi
Journal: International Journal of Surgery (2023)

Background: To compare the late outcomes between mechanical and bioprostheses after isolated mitral valve replacement (MVR) in dialysis-dependent patients. Methods: A nationwide propensity-matched retrospective cohort study was conducted involving dialysis patients who underwent primary mitral replacement between 2001 and 2018. Ten-year postoperative outcomes were compared between mitral bioprosthesis and mechanical prosthesis using the Cox proportional hazard model and restricted mean survival time (RMST). Results: The all-cause mortality was 20.8 and 13.0 events per 100 person-years, with a 10-year RMST of 7.40 and 7.31 years for bioprosthesis and mechanical prosthesis, respectively. Major bleeding was the most common adverse event for both bioprosthesis and mechanical prosthesis, with an incidence rate of 19.5 and 19.1 events per 100 person-years, respectively. The incidence of valve reoperation was higher among those who received bioprosthesis (0.55 events per 100 person-years). After 1:1 matching, the all-cause mortality was 15.45 and 14.54 events per 100 person-years for bioprosthesis and mechanical prosthesis, respectively. The RMST at 10 years was comparable between the two groups after matching (5.10 years for bioprosthesis vs. 4.59 years for mechanical prosthesis), with an RMST difference of −0.03. Further, no difference was observed in the incidence of major adverse valve-related events between bioprosthesis and mechanical valves. However, bioprosthesis was associated with a higher incidence of mitral valve reoperation among all major adverse events (RMST difference −0.24 years, 95% CI −0.48 to −0.01, P =0.047). Conclusions: This study found no association between valve selection and long-term survival outcomes in dialysis patients after MVR. However, bioprosthetic valves may be associated with a slightly higher incidence of reoperation, while other valve-related adverse events, including major bleeding and stroke, were comparable between the two types of prostheses.
Up-to-date molecular medicine strategies for management of ocular surface neovascularization
Authors: Yunlong Yang, Junmu Zhong, Dongmei Cui, Lasse D Jensen
Journal: Advanced Drug Delivery Reviews (2023)

Ocular surface neovascularization and its resulting pathological changes significantly alter corneal refraction and obstruct the light path to the retina, and hence is a major cause of vision loss. Various factors such as infection, irritation, trauma, dry eye, and ocular surface surgery trigger neovascularization via angiogenesis and lymphangiogenesis dependent on VEGF-related and alternative mechanisms. Recent advances in antiangiogenic drugs, nanotechnology, gene therapy, surgical equipment and techniques, animal models, and drug delivery strategies have provided a range of novel therapeutic options for the treatment of ocular surface neovascularization. In this review article, we comprehensively discuss the etiology and mechanisms of corneal neovascularization and other types of ocular surface neovascularization, as well as emerging animal models and drug delivery strategies that facilitate its management.
Association between a network-based physician linchpin score and cancer patient mortality: a SEER-Medicare analysis
Authors: Erika L Moen, Rachel O Schmidt, Tracy Onega, Gabriel A Brooks, A James O’Malley
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Patients with cancer frequently require multidisciplinary teams for optimal cancer outcomes. Network analysis can capture relationships among cancer specialists, and we developed a novel physician linchpin score to characterize “linchpin” physicians whose peers have fewer ties to other physicians of the same oncologic specialty. Our study examined whether being treated by a linchpin physician was associated with worse survival. Methods In this cross-sectional study, we analyzed Surveillance, Epidemiology, and End Results–Medicare data for patients diagnosed with stage I to III non-small cell lung cancer or colorectal cancer (CRC) in 2016-2017. We assembled patient-sharing networks and calculated linchpin scores for medical oncologists, radiation oncologists, and surgeons. Physicians were considered linchpins if their linchpin score was within the top 15% for their specialty. We used Cox proportional hazards models to examine associations between being treated by a linchpin physician and survival, with a 2-year follow-up period. Results The study cohort included 10 081 patients with non-small cell lung cancer and 9036 patients with CRC. Patients with lung cancer treated by a linchpin radiation oncologist had a 17% (95% confidence interval = 1.04 to 1.32) greater hazard of mortality, and similar trends were observed for linchpin medical oncologists. Patients with CRC treated by a linchpin surgeon had a 22% (95% confidence interval = 1.03 to 1.43) greater hazard of mortality. Conclusions In an analysis of Medicare beneficiaries with nonmetastatic lung cancer or CRC, those treated by linchpin physicians often experienced worse survival. Efforts to improve outcomes can use network analysis to identify areas with reduced access to multidisciplinary specialists.
Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes
Authors: Alexander Kutz, Dae Hyun Kim, Deborah J. Wexler, Jun Liu, Sebastian Schneeweiss, Robert J. Glynn, Elisabetta Patorno
Journal: Diabetes Care (2023)

To evaluate the comparative cardiovascular effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) in older adults with type 2 diabetes (T2D) across different frailty strata.
ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization
Authors: Agatha Schlüter, Valentina Vélez-Santamaría, Edgard Verdura, Agustí Rodríguez-Palmero, Montserrat Ruiz, Stéphane Fourcade, Laura Planas-Serra, Nathalie Launay, Cristina Guilera, Juan José Martínez, Christian Homedes-Pedret, M. Antonia Albertí-Aguiló, Miren Zulaika, Itxaso Martí, Mónica Troncoso, Miguel Tomás-Vila, Gemma Bullich, M. Asunción García-Pérez, María-Jesús Sobrido-Gómez, Eduardo López-Laso, Carme Fons, Mireia Del Toro, Alfons Macaya, Àngels García-Cazorla, Antonio José Ortiz-Martínez, Carlos Ignacio-Ortez, Cristina Cáceres-Marzal, Eduardo Martínez-Salcedo, Elisabet Mondragón, Estíbaliz Barredo, Ileana Antón Airaldi, Javier Ruiz Martínez, Joaquin A. Fernández Ramos, Juan Francisco Vázquez, Laura Díez-Porras, María Vázquez-Cancela, Mar O’Callaghan, Tamara Pablo Sánchez, Velina Nedkova, Ana Isabel Maraña Pérez, Sergi Beltran, Luis G. Gutiérrez-Solana, Luis A. Pérez-Jurado, Sergio Aguilera-Albesa, Adolfo López de Munain, Carlos Casasnovas, Aurora Pujol
Journal: Genome Medicine (2023)

Abstract Background Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. Methods We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient’s standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). Results ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. Conclusions ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.
Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China
Authors: Pei Wang, Hong-yi Zhang, Jixin Yang, Tianqi Zhu, Xiaojuan Wu, Bin Yi, Xiaoyi Sun, Bin Wang, Tao Wang, Weibing Tang, Hua Xie, Jinfa Tou, Yijiang Han, Xiang Liu, Jianghua Zhan, Yuanmei Liu, Yingchao Li, Zhibao Lv, Li Lu, Baohong Zhao, Tingliang Fu, Dianming Wu, Jianxi Bai, Wanfu Li, Heying Yang, Guofeng Zhang, Hongxia Ren, Jiexiong Feng
Journal: International Journal of Surgery (2023)

Background: Cholangitis is common in patients with biliary atresia following Kasai portoenterostomy (KPE). The prompt use of empiric antibiotics is essential due to the lack of identified microorganisms. The authors aimed to validate a severity grading system to guide empiric antibiotic therapy in the management of post-KPE cholangitis. Materials and methods: This multicenter, prospective, randomized, open-label study recruited patients with post-KPE cholangitis and was conducted from January 2018 to December 2019. On admission, patients were categorized into mild, moderate, and severe cholangitis according to the severity grading system. Patients in the mild cholangitis group were randomized to receive cefoperazone sodium tazobactam sodium (CSTS) or meropenem (MEPM). Patients with severe cholangitis were randomized to treatment with MEPM or a combination of MEPM plus immunoglobulin (MEPM+IVIG). Patients with moderate cholangitis received MEPM. Results: The primary endpoint was duration of fever (DOF). Secondary outcomes included blood culture, length of hospital stay, incidence of recurrent cholangitis, jaundice clearance rate, and native liver survival (NLS). For mild cholangitis, DOF, and length of hospital stay were similar between those treated with CSTS or MEPM (all P &gt;0.05). In addition, no significant difference in recurrence rate, jaundice clearance rate, and NLS was observed between patients treated with CSTS and MEPM at 1-month, 3-month, and 6-month follow-up. In patients with moderate cholangitis, the DOF was 36.00 (interquartile range: 24.00–48.00) h. In severe cholangitis, compared with MEPM, MEPM+IVIG decreased DOF and improved liver function by reducing alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin at 1-month follow-up. However, recurrence rate, jaundice clearance rate, and NLS did not differ significantly between MEPM+IVIG and MEPM at 1-month, 3-month, and 6-month follow-up. Conclusions: In patients with post-KPE cholangitis, MEPM is not superior to CSTS for the treatment of mild cholangitis. However, MEPM+IVIG treatment was associated with better short-term clinical outcomes in patients with severe cholangitis.
What happens inside a long covid clinic?
Authors: Erin Dean
Journal: BMJ (2023)

Close to 100 NHS long covid clinics have sprung up. Erin Dean visits one and meets a multidisciplinary team tailoring support for this wide ranging and poorly understood condition When 60 year old Shelley Curran caught covid-19 in autumn 2020, she waited to feel better. And waited. While her husband, who has chronic obstructive pulmonary disease, recovered well, her symptoms dragged on. "I just never really got better," she says. "I stayed breathless and I was fatigued—and then new symptoms came along to join the ones I already had. I can only do something for 10 to 15 minutes and then I have to stop to recover. People, even GPs, think you're making it up." Curran, who lives in Wokingham, has had four appointments with the long covid assessment clinic at the Royal Berkshire NHS Foundation Trust in Reading. She has had many symptoms including brain fog, digestive problems, nausea, pins and needles, feeling lightheaded, and shoulder and hip pain. She is one of 2300 patients the clinic—which is part of the Berkshire Long Covid Integrated Service run by the acute and local community trust—has seen to provide an assessment and management plan. It is one of a national network of services announced by NHS England in December 2020 to support those struggling with the condition (see box 1).1 Box 1 ### Defining long covid Some 1.9 million people in the UK—almost 3% of the population—were estimated to have long covid this March, according to self-reported data analysed by the Office for National Statistics.2 One in five of those affected said their ability to undertake daily activities had been "limited a lot" by symptoms continuing for more than four weeks. These symptoms are wide ranging and often fluctuating, according to joint guidance from the National Institute for Health and Care Excellence (NICE), Royal … RETURN TO TEXT
Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial
Authors: Qi-Feng Chen, Ning Lyu, Xun Wang, Xiong-Ying Jiang, Yue Hu, Song Chen, Sui-Xing Zhong, Zi-Lin Huang, Minshan Chen, Ming Zhao
Journal: International Journal of Surgery (2023)

Objectives: The phase III FOHAIC-1 trial revealed that hepatic arterial infusion of chemotherapy (HAIC) improved overall survival compared to sorafenib in the high-risk hepatocellular carcinoma (HCC). This study therefore set out to evaluate the cost-effectiveness and establish a prognostic clinico-radiological score of HAIC. Materials and methods: A total of 409 patients with high-risk HCC who received HAIC between 2014 and 2020 were included. A Markov model was applied in the cost-effectiveness analysis using data from the FOHAIC-1 trial. In prognosis analysis, a clinico-radiological score was developed using a Cox-regression model and subsequently confirmed in the internal validation and test cohorts. The area under the curve from receiver operator characteristic analysis was used to assess the performance of the clinico-radiological score. Results: HAIC resulted in an incremental cost-effectiveness ratio of $10190.41/quality-adjusted life years compared to sorafenib, which was lower than the willingness-to-pay threshold. Probabilistic sensitivity analysis predicted a ≥99.9% probability that the incremental cost-effectiveness ratio was below the willingness-to-pay. The Cox analysis identified five factors, namely extrahepatic metastasis (m), arterial enhancing type (a), tumor number (nu), albumin-bilirubin index (a), and involved lobe (l), which together comprise the clinico-radiological score (HAIC-manual). Patients were classified into three groups based on the number of factors present, with cutoffs at 2 and 4 factors. The stratified median overall survival for these groups were 21.6, 10.0, and 5.9 months, respectively ( P &lt;0.001). These findings were verified through internal validation and test cohorts with a significance level of P ≤0.01. The time-dependent area under the curve from receiver operator characteristic for the ability of the HAIC-manual to predict survival in 1, 2, and 3 years were 0.71, 0.76, and 0.78, which significantly outperformed existing staging systems. Conclusion: HAIC is a promising and cost-effective strategy for patients with high-risk HCC. The clinico-radiological score may be a simple prognostic tool for predicting HAIC treatment.
Heterogeneity in allospecific T cell function in transplant-tolerant hosts determines susceptibility to rejection following infection
Authors: Christine M. McIntosh, Jennifer B. Allocco, Peter Wang, Michelle L. McKeague, Alexandra Cassano, Ying Wang, Stephen Z. Xie, Grace Hynes, Ricardo Mora-Cartín, Domenic Abbondanza, Luqiu Chen, Husain Sattar, Dengping Yin, Zheng J. Zhang, Anita S. Chong, Maria-Luisa Alegre
Journal: Journal of Clinical Investigation (2023)

Even when successfully induced, immunological tolerance to solid organs remains vulnerable to inflammatory insults, which can trigger rejection. In a mouse model of cardiac allograft tolerance in which infection with Listeria monocytogenes (Lm) precipitates rejection of previously accepted grafts, we showed that recipient CD4+ TCR75 cells reactive to a donor MHC class I-derived peptide become hypofunctional if the allograft is accepted for more than 3 weeks. Paradoxically, infection-induced transplant rejection was not associated with transcriptional or functional reinvigoration of TCR75 cells. We hypothesized that there is heterogeneity in the level of dysfunction of different allospecific T cells, depending on duration of their cognate antigen expression. Unlike CD4+ TCR75 cells, CD4+ TEa cells specific for a peptide derived from donor MHC class II, an alloantigen whose expression declines after transplantation but remains inducible in settings of inflammation, retained function in tolerant mice and expanded during Lm-induced rejection. Repeated injections of alloantigens drove hypofunction in TEa cells and rendered grafts resistant to Lm-dependent rejection. Our results uncover a functional heterogeneity in allospecific T cells of distinct specificities after tolerance induction and reveal a strategy to defunctionalize a greater repertoire of allospecific T cells, thereby mitigating a critical vulnerability of tolerance.